Good afternoon, everyone, and welcome to the next session in our series of presentations. Welcome to the 27th Annual H.C. Wainwright Global Investment Conference. My name is Matt Keller. I'm a Vice President in the Equity Research Department, and it is now my pleasure to introduce our next presenter. On stage, we have CEO Thane Wettig of FibroGen. Thane, please take it away.
Matt, thank you, and thanks to H.C. Wainwright for the presentation opportunity. I'm also joined here by David DeLucia, who is our CFO, and I'd be happy to take any questions after the presentation. I have a tendency to speak fast, and given the amount of material to cover, I probably will speak extra fast, so apologies ahead of time. The obligatory forward-looking statements. But really, when you think about the investment thesis for FibroGen, there are a couple of programs that we're really excited about going forward. The first thing is, a little less than two weeks ago, we completed a transformative sale of our FibroGen China operations to AstraZeneca, our longstanding partner in China, for a total consideration of approximately $220 million. This extends our cash runway into 2028 and, importantly, allowed us to pay off our term loan with Morgan Stanley Tactical Value.
So it simplifies our capital structure in a significant way. That now allows us to turn our focus and our attention to our two programs. The first is an ADC that targets a unique epitope on the surface of prostate cancer cells called CD46. It's an antibody-drug conjugate with meaningful responses that we've seen in a phase one monotherapy trial that we'll speak about in a moment. This program also has a companion PET imaging agent that also targets CD46 that can be a potential patient selection biomarker that we're going to investigate as part of the phase two monotherapy program as well. Our second opportunity is roxadustat. Roxadustat has been approved in more than 40 markets. Roxadustat was the asset that we sold to AstraZeneca in China.
They received a complete response letter for anemia associated with chronic kidney disease in the United States in the fall of 2021, and now we've shifted the attention. Now that we got the license back from AstraZeneca in the US and other markets, we've shifted our attention to the potential to study roxadustat in a phase three trial in anemia associated with lower risk myelodysplastic syndrome. We had a successful type C meeting with the FDA recently and aligned on a number of the design elements for the phase three trial and anticipate submitting the phase three protocol in the fourth quarter of this year, with the potential to start a phase three trial for roxadustat in anemia associated with lower risk myelodysplastic syndrome in 2026.
So we've got a number of near-term catalysts that, again, we're excited about the initiation of the phase two monotherapy trial for our ADC targeting CD46 and the companion PET imaging agent, with expected interim results sometime in the second half of 2026. We'll see top-line results from the phase two portion of an ongoing IST at UCSF of the ADC in combination with enzalutamide in MCRPC. We should see that data toward the end of this year, and then the potential for the phase three protocol submission and a phase three initiation for roxadustat, the protocol submission in the fourth quarter of this year, and then the potential to start that trial sometime in 2026. And we're going to go into both of these programs in a bit of detail for those that aren't necessarily aware of both programs.
Don't want to say, don't need to say a lot of things about prostate cancer other than the fact that there continues to be a significant unmet need in metastatic castration-resistant prostate cancer. We hear oftentimes, well, it's a really competitive space, which is true, but it's a competitive space that still sees the disease progress and still has a significant opportunity for new novel therapies and, in our case, a non-PSMA approach to treating MCRPC. And we think it can also be well-informed with a patient selection biomarker, which is part of our phase two program, which we'll talk about in a moment. Our target is a non-PSMA approach. It's CD46, which is a novel tumor selective target in solid tumors. Seen it expressed on the surface of prostate cancer cells, colorectal cancer, and some other solid tumors.
That's a multifunctional protein which negatively regulates the complement system and helps tumors evade the complement-dependent cytotoxicity. It's overexpressed in MCRPC. The CD46 expression is upregulated as prostate cancer progresses from the castration-sensitive phase to the castration-resistant phase. CD46 is also then further overexpressed following treatment with ARSIs. Our best characterization of the target itself is that the majority of patients with prostate cancer do express CD46. We think that the high level of expression occurs in about 50%-70% of patients. So there's a great opportunity to further characterize that through the conduct of our phase 2 trial. In addition to the expression being upregulated as well as prostate cancer progresses, CD46 is also overexpressed more homogenously and at higher levels compared to PSMA.
Again, based upon the results that we'll talk about in a moment of the phase one monotherapy trial, we know the target's active, and we know that the antibody, along with the MMAE payload that's part of our ADC complex, we know that it is active as well. There's two components to the program. There's the therapeutic, and there's a PET imaging agent. Our therapeutic has a targeting antibody that, again, targets CD46 along with an MMAE payload, again, a very well-characterized payload in use in other oncology therapies. This is an androgen receptor agnostic and a non-PSMA approach, which we think is important to keep in mind.
And then with the PET-3180 imaging agent, it utilizes the same targeting antibody as does FG3246 with the zirconium tracer, and we believe it has the potential to inform patient selection as we progress the program through the phase two and phase three stages. The data that we have shared previously in monotherapy in phase one demonstrated 8.7 months of median RPFS. We think that's very competitive, and we'll show a chart here in a moment of how we think that stacks up relative to other earlier stage programs. We saw a 36% PSA 50 response, an ORR of 20%. All five of those patients were at the 2.7 milligram per kilogram dose, which was a dose used in the expansion phase, and a median duration of response of 7.5 months.
In terms of how that compares with a couple of other programs, which you may be familiar with, an Amgen program as well as Janux, different numbers of patients being treated. Obviously, we want to make sure that we caveat this that it's difficult to do comparisons from one trial to the next based upon differences in the design and enrollment and patient characteristics. But when we look at the 8.7 months that we've seen in the monotherapy phase 1 trial relative to the Amgen and the Janux data that have been reported, we think we compare very favorably relative to those other two earlier stage programs. There's also an IST going on at UCSF that's now, it's a phase 1/2 program. It's in the phase 2 portion of that, so it's in the expansion portion. 17 patients were treated in the phase 1 portion of the trial.
There was a median RPFS of 10.2 months. We will see data on all 41 patients as a part of this IST sometime toward the back part of this year. And again, this is in combination with enzalutamide. So as compared to the phase two trial, which we are planning on starting imminently, which is a monotherapy design, this particular trial is in combination with enzalutamide, which we think gives us some potential optionality as we think about the go-forward for the program. This is another chart that compares the results that we've seen in both the monotherapy as well as the combination therapy trials relative to other programs in kind of second line and beyond therapies for later stage trials with the same caveats that you can't necessarily do a direct-to-direct comparison.
But this is the data that continues to have us excited about the potential for this program going forward. The phase 2 design, 75 patients, 25 patients in each one of three dose cohorts. We use the exposure response from the phase 1 monotherapy trial to inform then the three doses that were selected here. We'll see an interim analysis in the second half of next year with a final analysis then approximately 12 months after that. Importantly, an important design element of this trial is the use of primary prophylaxis with G-CSF to mitigate against the neutropenia that was seen in the phase 1 monotherapy trial. So a number of the patients at the 2.7 milligram per kilogram dose that was the dose for the expansion phase had to be either dose interrupted or downward titrated because of neutropenia, primarily grade three and above neutropenia. Dr.
Rahul Aggarwal, who was the PI of the monotherapy trial, is also the lead for the IST that's ongoing at UCSF in combination with enzalutamide. He has utilized that approach, prophylaxis with G-CSF in his expansion cohort, and has seen very good results in terms of a sizable reduction in the incidence of grade three or above neutropenia and has seen very little dose reduction or dose interruption, and so we're going to employ that same approach in our phase two design, so when we think about how do we potentially build upon the 8.7 months of RPFS that was seen in the phase one monotherapy trial, in addition to the utilization of G-CSF as prophylaxis against neutropenia, we are using three of the higher doses that were seen in the phase one monotherapy trial based upon the exposure response analysis we conducted.
Then we're also going to be studying patients who are earlier line in terms of prostate cancer progression. Median of five prior lines of therapy in the phase one monotherapy trial. We're going to be looking at patients who are going to be either first line or second line post-ARSI, but in that pre-chemo setting. We think that this gives us some pretty important optionality as we go forward. With the phase two monotherapy trial designed to select the dose that we would then take into phase three, along with the potential for combination therapy with an ARSI, we think it could potentially unlock multiple registration pathways that would either be sequentially or in parallel with multiple lines of therapy in prostate cancer, either monotherapy and/or combination therapy, and either in an all-comers population or in those patients who have higher expression of CD46.
Near-term catalysts. We got the IND cleared for the PET imaging agent last quarter. We initiate the phase two monotherapy trial in this quarter, so in the coming few weeks. In the fourth quarter of this year, we will see top-line results from the IST that's ongoing at UCSF, and then the second half of next year, we'll see interim analysis from the phase two monotherapy trial, so in summary, we believe we have a novel mechanism of action with a potential first-in-class opportunity. Nobody else is working on CD46 as a target. We've seen what we believe to be very encouraging results in the two phase one studies. We have a well-characterized safety profile associated with the MMAE payload, and again, significant opportunity given the unmet need in MCRPC, along with the opportunity to combine a PET imaging agent as part of the program, so then shifting to Roxadustat.
Again, I stated Roxadustat has been approved in more than 40 countries for anemia associated with chronic kidney disease. It's a natural way to increase hemoglobin by mimicking the body's natural response to low oxygen, and in fact, this science was the basis for the 2019 Nobel Prize in Physiology and Medicine for the discovery of how cells sense and adjust and adapt to oxygen availability, so we know Roxadustat increases hemoglobin. We know that it's been approved in more than 40 markets for anemia associated with chronic kidney disease, and now we're going to be studying it in a late-stage trial for anemia associated with lower risk myelodysplastic syndrome. It's an orphan disease here in the U.S. 90% of the patients who have MDS suffer from anemia. The current first-line and second-line therapies are effective, but there still is a lot of room for opportunity.
Transfusion independence is the primary marker associated with lower risk myelodysplastic syndrome. The therapies that are approved have demonstrated a transfusion independence in less than 50% of patients. So there still is a substantial unmet need. Importantly, the current standards of care have some challenges in terms of calibrating the dose and challenges in terms of administration in office, either IV infusion or subcutaneous injection. Roxadustat would be an oral option three times a week that could be taken at home, which from what the KOLs tell us would be a meaningful opportunity for a number of these patients who tend to be 70 years of age or older and in fairly progressed status in terms of health and to have an at-home option. The KOLs tell us that that's an important opportunity. The market is very well characterized.
EvaluatePharma projects that this market of lower risk myelodysplastic syndrome will exceed $4 billion by 2030. BMS has guided to luspatercept peak sales in 2030 of over $4 billion. So the EvaluatePharma projection is likely on the low side. When we take a look at the proof of concept that we have with roxadustat in lower risk myelodysplastic syndrome, we ran a previous phase three trial in this condition. We showed a numerical advantage in terms of transfusion independence relative to placebo, but we didn't reach statistical significance. The reason we missed it on the statistical side was because the placebo response was higher than had been seen in any of the other lower risk MDS trials. And the reason the placebo response was so high was because there were a number of patients who were enrolled that have a low transfusion burden at baseline.
When we went back into the subgroup analysis post-hoc on patients who had what's defined by the International Working Group as a high transfusion burden at baseline, we saw a nominally statistically significant effect, 36% transfusion independence at eight straight weeks for roxadustat relative to 7% for placebo within the first 28 weeks of the trial. You can see then that those results actually were enhanced when we take a look at eight-week transfusion independence throughout the course of the 52-week trial. This is what gives us a lot of excitement about the potential for a phase three trial in this particular patient population.
I think it's important to point out that with that 36% transfusion independence response versus 7% for placebo, when you compare that to the two recently approved products and their registrational trials, you can see in that same patient population, the patients with a higher transfusion burden at baseline, you can see that the results are very similar across the programs. We believe that we have the opportunity to elevate the standard of care in second line and beyond lower risk myelodysplastic syndrome. Luspatercept is recommended as a first-line therapy in RS positive patients. ESAs and luspatercept are recommended as first-line therapies in RS negative patients. Imetelstat was approved about a year ago. They have now been introduced into the guidelines.
From what we hear from KOLs is that the use of an imetelstat is definitely after ESAs and luspatercept and the fact that based upon some of the challenging aspects of an imetelstat from an administration as well as an evaluation perspective, they have not achieved what many thought that they would be able to achieve, which again gives us, we believe, a real opportunity in the second line and beyond setting. We did reach alignment in our Type C meeting with the FDA on a number of the design elements of the phase three trial. The patient population is high transfusion burden population of four or more units of RBCs over two consecutive eight-week periods of time prior to enrollment in the trial. These are patients who are going to be refractory to, intolerant to, or ineligible for ESAs.
They may or may not have been on luspatercept as well, but they will not have been on imetelstat for entry into our trial. We're still working through whether the transfusion independence and primary endpoint will be eight weeks or 16 weeks, and that the final analysis will be performed when all the patients have completed 12 months of trial or have discontinued. On the safety side, the feedback from the FDA based upon the Complete Response Letter for roxadustat in the anemia of CKD program was that we want to make sure that you guys mitigate against thrombotic risk, which we clearly are based upon eligibility criteria and dose modification criteria based upon the titration after the starting dose.
We did align with the agency, and this was an important consideration for us on using the same starting dose for this upcoming phase three trial that was used in the previous phase three trial and with the ability to titrate up to a maximum of three and a half milligrams per kilogram. Importantly, we anticipate submitting the final protocol to the FDA in the fourth quarter of this year with the intention to start a phase three program in 2026. We're going to be looking at the opportunity to develop this asset on our own as well as partner it. We'll ultimately make the decision that we believe is in the best interest of stakeholders as it relates to how we choose to proceed.
We think that it is easily achievable for more than $500 million in peak US sales for this particular asset in low-risk myelodysplastic syndrome. Last thing to cover is just a bit more detail on the sale of FibroGen China to AstraZeneca. There's an enterprise value of $85 million. There was approximately $135 million FibroGen cash held in China at closing that AZ has now paid us for. The net cash payable at closing is subject to a $10 million holdback from AstraZeneca that we would anticipate receiving a portion or all within the next nine months or so. We did complete the sale less than two weeks ago.
As I stated earlier, we successfully paid off the term loan with MSTV, simplifying our capital structure, getting rid of a significant overhang in terms of the $75 million of debt that was on our balance sheet. And importantly, we now have a cash runway that is extended into 2028. So in summary, we're very excited about the prospects of FG3246 and the companion PET imaging agent for MCRPC and the upcoming start of the phase two monotherapy trial. We're also working hard to ensure that we submit the phase three protocol for roxadustat for lower risk MDS in the fourth quarter of this year while we evaluate the internal development opportunity as well as partnering opportunities with the intention to start a phase three trial sometime in 2026. Thank you all for your time.
Take a moment. Thank Thane and the FibroGen team for the excellent presentation.
As they mentioned, if you do have any follow-up questions, we encourage you to follow up after the session at the conference. Otherwise, thank you again, and thank you everyone for attending the conference this year. Appreciate it.